A Rare Case of Adult-Onset Rectosigmoid Hypoganglionosis

Background

Intestinal innervation disorders represent a cluster of malformations of the intestinal nervous system and include intestinal neuronal dysplasia, Hirschsprung’s disease, hypoganglionosis, and ganglioneuromatosis [1–3]. Although these subtypes have distinct histopathological features, clinical manifestations are similar with chronic constipation or pseudo-obstruction being the most common presenting symptoms [1,2]. Differential diagnosis includes chronic intestinal pseudo-obstruction (CIPO) that can be associated with visceral myopathies and mutations of the ACTG2 gene involved in myenteric contractility [4]. Hypoganglionosis is divided into 2 types: the isolated and Hirschsprung-associated form [5]. Isolated hypoganglionosis is rare, representing 3% to 5% of all congenital intestinal neurological diseases [6]. The histopathological features include hypertrophy of the muscularis mucosae, decrease in the activity of acetylcholinesterase in the lamina propria, and significant reduction in the number of myenteric ganglia. Diagnosis and ability to differentiate between different patterns of innervation is based on histopathology and immuno-histochemical markers [5,6]. The disease most commonly present in infancy or childhood with only a few cases reported in adults mainly diagnosed after elective surgery for intractable constipation or pseudo-obstruction [7,8]. The authors report a case of isolated hypoganglionosis in an adult presenting as an emergency; we also provide a review the literature.

Case Report

A 20-year-old male Saudi patient presented to the Emergency Department complaining of severe abdominal pain, obstipation, vomiting, shortness of breath, and palpitations. Past history revealed intermittent constipation since early childhood that had never been investigated and self-treatment with on and off use of laxatives. No symptoms of urinary dysfunction or infections were reported. He had no co-morbidities and was not on any medication. Family history was unremarkable. On examination, the patient was tachycardic (heart rate, 140 beats per minute), hypertensive (blood pressure, 146/92 mmHg), and tachypneic (respiratory rate, 23 breaths per minute). The abdomen was grossly distended with rebound tenderness and bowel sounds were scant. Fluid resuscitation and oxygen administration were initiated. A nasogastric tube and urinary catheter were inserted. Blood tests revealed a leukocyte count of 12 900 cells/μL and blood gas levels showed mild respiratory alkalosis. Acute x-ray series showed large-bowel dilatation with multiple air-fluid levels (Figure 1). A computed tomography (CT) scan of the abdomen and pelvis revealed gross dilatation of the sigmoid and rectum with a diameter up to 20 cm with a functional obstruction at the level of the lower rectum. No wall thickening, peri-colonic stranding, pneumatosis, or pneumoperitoneum were noted. There was significant stool volume throughout. The small bowel and urinary bladder were displaced by the distended colon to the right, with the liver and gallbladder being displaced posteriorly (Figure 2). An emergency laparotomy was performed, and this revealed a redundant megasigmoidand rectum (Figure 3). A rigid sigmoidoscopy was carried out and showed only fecal impaction with no evidence of obstructing lesions. A Hartmann’s procedure was performed. The patient made a slow but uneventful recovery and was discharged on the 12th postoperative day. Histopathological examination of the resected specimen showed features consistent with hypoganglionosis. The ganglion cells were reduced but normal with no signs of degeneration or gliosis (Figure 4A–4C). The muscularis mucosa was unremarkable with absence of atrophy, vacuolar degeneration, fibrosis, and normal collagenous network raising no suspicion of myopathy (Figure 4D). The proximal resection margin showed normal ganglia distribution. At 2 months from the surgery, full thickness rectal biopsies were taken under general anesthesia just above the dentate line for further characterization of the innervation disorder. Histology of the rectal specimen confirmed the diagnosis of hypoganglionosis with no evidence of agangliosis. The patient was reluctant to undergo definitive surgery and at 1-year follow-up had no complaints with a perfectly functioning colostomy.

Discussion

The most common intestinal innervation disorder is Hirschspung’s disease with a reported prevalence of 1: 5000 and a female to male ratio of 1: 4 [9]. The disease is characterized by the congenital absence of ganglion cells in the submucosal and myenteric neural plexuses of the rectal wall with variable extension proximally. Etiology is represented by impaired craniocaudal migration of neuroblasts during the first 3 months of gestation [10,11]. The transition of the distal aganglionic segment to the proximal normal bowel may be characterized by a segment of hypoganglionosis with maintained but reduced number of ganglia [11,12]. A number of ganglia less than 10 mm is generally considered diagnostic for hypoganglionosis [13]. Isolated hypoganglionosis not related to Hirschsprung’s disease is a distinct and rare disorder. In this variety, the submucosal nerve plexus is normal while a significant reduction in the myenteric ganglia is noted. Other features include hypertrophy of the muscularis mucosae and decreased acetylcholinesterase activity in the lamina propria [5,6]. In congenital hypoganglionosis, the number and size of ganglion cells is reduced at birth, and although their size increases with time, their number does not change. On the other hand, acquired hypoganglionosis is of late onset and characterized by a degeneration of ganglion cells and histological findings of gliosis [13]. Histological examination of full-thickness rectal biopsies is the gold standard for diagnosis. Hematoxylin and eosin stain is most commonly used and allows for diagnosis in most cases. However, morphologic immaturity and small size of ganglion cells with irregular distribution in the submucosa may limit identification with high expertise needed. Also, acetylcholinesterase staining is technically demanding and not universally available [14]. More recently peripherin, S-100, and Calretinin immunohistochemistry have been shown to be a valuable tool to aid diagnosis [14–16]. Hypoganglionosis should be distinguished by cases of CIPO related to visceral myopathy that can be associated with mutations of the ACTG2 gene mutations involved in muscle contractility. In these cases, a family history is often positive, functional dysfunction of other organs is common as well as pathological features of the muscularis propria including vacuolization and fibrosis [4]. A recent review of the literature identified 92 patients with a diagnosis of isolated hypoganglionosis (69 males and 23 females with a mean age of 4.85 years) [6]. Symptoms at presentation included chronic constipation or pseudo-obstruction. Only 70% of these patients had surgical intervention at the time of presentation and of these 80% had definitive surgery with pull-through procedures and 16% stoma formation. The overall mortality was 8%. A recent nationwide study in Japan reported 109 cases of isolated hypoganglionosis and provided detailed information on 90 patients (34 males and 56 females) with 19 being excluded from the study for diagnostic doubt or incomplete descriptions [17]. The diagnosis was made in the neonatal period in all patients. Almost all patients were initially treated with formation of stoma. Creation of a jejunostomy was significantly associated with a lower mortality. The overall mortality rate was 22%. A study from South Korea reported 24 cases of adult presentation of hypoganglionosis in patients who had undergone surgery for intractable constipation or chronic pseudo-obstruction. The mean age was 40 years [8]. There are only 5 other cases in the literature with adult presentation of hypoganglionosis as an emergency [7,18–21]. Paucity and intermittence of symptoms had allowed for a late diagnosis and ultimate acute presentation. Three of these case presented with toxic megacolon, 1 with phytobezoar obstruction and 1 with sigmoid volvulus. In our case, the initial sigmoid resection had shown hypoganglionosis with normal proximal resection margin. Subsequent rectal biopsies excluded agangliosis and confirmed hypoganglionosis. A functional obstruction seen on pre-operative CT scan is a common finding in these patients and usually associated with a greater reduction of ganglion cells at the level of the transition zone [8].

Conclusions

Isolated hypoganglionosis is very rare and a high index of suspicion is required in young patients with prior history of chronic constipation to avoid delayed diagnosis and emergency presentation. Histopathology and immunohistochemistry allow differentiation among the various patterns of innervation disorders. Acute presentation with need of emergency surgery is rare and treatment should be limited to colonic resection with subsequent definitive treatment of the rectal disease.